In the discussion, the expert panel raised a question about tailoring weight loss to personalize type 2 diabetes prevention. It explored the significance of polygenic scores versus adiposity measures in predicting diabetes development. It was noted that polygenic scores are relatively crude instruments encompassing various pathways leading to a disease without providing explicit information on causation or potential benefits from specific interventions. Specifically, comparing polygenic scores for BMI with those for diabetes revealed that BMI scores lack validity as genetic instruments due to the correlation between variants. Therefore, the discussion emphasized the importance of considering both measured adiposity and instrumental genetic variables for causal effects. Another aspect addressed was the difference in the impact of lifelong exposure to adiposity compared to LDL cholesterol or systolic blood pressure. It was suggested that while LDL cholesterol and blood pressure have significant effects due to accumulating irreversible structural damage to the artery wall over time, adiposity does not lead to such irreversible injury. Instead, reversible changes in adiposity indicate different biology, allowing for interventions to target weight loss at a later stage when needed. This contrast underscores the necessity to start early intervention for LDL cholesterol and blood pressure, whereas interventions for diabetes can be initiated when deemed necessary based on individual circumstances.

American College of Cardiology (ACC) Congress 2024, 6th April – 8th April 2024, Atlanta, Georgia, USA